Genetic risk for anhedonia linked to altered brain activity during reward processing

A study in Germany found that individuals with higher polygenic risk scores for anhedonia showed specific patterns of brain activity when processing anticipated monetary rewards. More specifically, they showed decreased activation in the bilateral putamen and left middle frontal gyrus during anticipation of rewards and decreased activation in the right caudate while receiving feedback. The research was published in the Journal of Affective Disorders.

Anhedonia is the reduced ability to experience pleasure or interest in activities that are normally rewarding. It is a core symptom of major depressive disorder but also appears in other conditions such as schizophrenia, substance use disorders, and bipolar disorder.

Anhedonia can involve diminished pleasure during activities (consummatory anhedonia) or reduced motivation and anticipation for rewards (anticipatory anhedonia). People with anhedonia may withdraw from social interactions, hobbies, or goals they once enjoyed. Neurobiologically, it is linked to dysfunction in brain reward systems, particularly pathways involving dopamine.

Psychological factors such as chronic stress, trauma, and negative cognitive patterns can contribute to its development. Anhedonia is associated with poorer quality of life and worse clinical outcomes when it persists. It can make treatment more challenging because reduced motivation may limit engagement in therapy or daily activities.

Study author Nicholas Schäfer and his colleagues investigated the role of a polygenic risk score for anhedonia in functional brain activity during the monetary incentive delay (MID) task. The MID task is a paradigm that requires participants to respond quickly to cues signaling potential monetary gains or losses. A polygenic risk score is an estimate of an individual’s genetic predisposition to a trait or disorder created by aggregating the effects of many genetic variants across the genome.

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Study participants were individuals participating in the MooDs and IntegraMent studies. These were multisite neuroimaging studies recruiting a total of 974 individuals; this specific study analyzed data from 517 of them. The sample included 57 patients with major depressive disorder, 39 with schizophrenia, and 48 with bipolar disorder. The remaining 373 participants were healthy controls (a group that included 243 healthy individuals and 130 healthy first-degree relatives of patients).

Study authors calculated participants’ polygenic risk scores for anhedonia using their genotype data. They also assessed participants’ anhedonia scores using a questionnaire (derived from the SCL-90). Participants completed the monetary incentive delay task while undergoing functional magnetic resonance imaging (fMRI) of their brains. In this task, participants were presented with arrows that indicated either a potential monetary reward, a potential loss, no reward, or a cue for verbal trials. This was the anticipation phase.

Participants then had to react to a visual target by pressing a button (except in the neutral trials where no action was required). After this, they received feedback about whether they lost or won 2 EUR, or received neutral or verbal feedback (e.g., “You reacted slow”). This was the feedback phase of the task.

Results showed that individuals with higher polygenic risk scores for anhedonia tended to show decreased activation in the putamen region of the brain in both brain hemispheres and in the left middle frontal gyrus during the anticipation phase of the task. They also showed lower activation in the right caudate region during the feedback phase (specifically during reward feedback).

Participants with higher polygenic risk scores for anhedonia also tended to show lower activity in the left middle frontal gyrus while anticipating financial loss and during salience processing (deciding how important the events at hand are).

However, while participants were receiving feedback about losing 2 EUR, individuals with higher polygenic risk scores for anhedonia tended to show heightened activity in the bilateral putamen and right caudate regions.

The right caudate nucleus of the brain is involved in goal-directed behavior, reward-based learning, and the integration of motivation with action selection, while the left middle frontal gyrus supports executive functions such as working memory, planning, and top-down cognitive control. The putamen primarily contributes to motor control and habit formation, and it also plays a role in reinforcing learned actions through reward processing.

“Our results highlight the importance of the striatum and prefrontal cortex in the context of a genetic risk for anhedonia,” the study authors concluded.

The study contributes to the scientific understanding of the neural basis of anhedonia. However, it should be noted that studies of neural correlates of psychological characteristics often yield inconsistent results. There are often pronounced individual differences in brain activities associated with specific psychological characteristics. Further studies are needed to verify and corroborate the reported findings.

The paper, “Associations between polygenic risk for anhedonia and functional brain activity during reward processing,” was authored by Nicholas Schäfer, Swapnil Awasthi, Stephan Ripke, Anna Daniels, Andreas Meyer-Lindenberg, Heike Tost, Andreas Heinz, Henrik Walter, and Susanne Erk.